Abstract
Introduction: Inborn errors of amino acid (AA), organic acid (OA) metabolism and disorders of the urea cycle (UCD) represent a heterogeneous group of 135 different diseases caused by impaired synthesis, transport or degradation of AA, OA and ammonia. Individual diseases are rare, but the overall incidence in the population is 1:3000-4000.
Methodology: The work summarizes the clinical, diagnostic and therapeutic aspects of the most common inborn errors of AA, OA metabolism and UCD. Eight diseases are part of laboratory neonatal screening, diagnosis of other IEMs depends on clinical suspicion, determination of ammonia in the blood and rapid indication of selective metabolic screening.
Results: Inborn errors of AA, OA metabolism and UCD are clinically manifested by acute or subacute metabolic disruption with metabolic alkalosis or acidosis and subsequent hepatic, renal and / or cerebral impairment or slowly progressive brain impairment with developmental delay and cognitive decline. The first group includes OA, tyrosinemia type 1, leucinosis and UCD, which are manifested by the accumulation of toxic metabolites arising from amino acid degradation. The second group includes phenylketonuria and homocystinuria, which are associated with eye, bone and / or thromboembolic events.
Conclusion: Adequate therapy depends on early diagnosis. Elimination methods are used in patients with acute brain involvement, such as severe hyperammonaemia. In patients with chronic disease, a lifelong low-protein diet supplemented with foods for special medical purposes, vitamin therapy and chaperone therapy supporting the activities of affected enzymes and efforts to block or activate alternative metabolic pathways are used. The number of diseases in which enzyme replacement therapy or liver or kidney transplantation is used is increasing. Trials with gene therapy are underway.